584,341. That’s the number of unread emails in my in-box as of this morning. There’s simply no way I’m going to dig myself out, and I’m fast approaching what many others do at this point: Declare “email bankruptcy” by marking them all as read, and start from scratch. I’m not the only one in this situation. According to McKinsey, we spend nearly one-third of our workweek managing email.

Several startup companies with talkative titles—Yammer, Chatter, Convo, HipChat—have sprung up in recent years to openly wage war on email. With inter­faces inspired by today’s social networks, their software aims to replace email, which was designed to be asynchronous, with real-time communication tools that can be as broad or focused as needed. Businesses certainly seem to like the idea: In 2012, Microsoft MSFT paid $1.2 billion for Yammer, which is used by Shell, Capgemini, and Nationwide, and investors value HipChat parent Atlassian at more than $3.3 billion. (The startup counts Netflix NFLX , Dropbox, and Intuit INTU as customers.)

Illustration by Pablo Bernasconi for Fortune

Yet we continue to spend more time in our in-box. Even Stewart ­Butterfield, the founder of Slack, another email killer with an almost $3 billion valuation, says he spends three to four hours a day sifting through email. His unread-email count: 16,000.

Are we waging a war that has no chance of being won?

What we now know as email began in 1971. A team of computer programmers at Bolt Beranek and Newman (now BBN Technologies) in Cambridge, Mass., had begun experimenting with internal messaging. One of them, Ray Tomlinson, had an idea to send a text message between computers using a new network called Arpanet, routing it using an “@” symbol. It worked. By the 1980s government and military personnel were actively using the system. By the 1990s email had become one of two pillars of the budding consumer Internet, alongside the World Wide Web.

Email promised efficiency and simplicity. But Tomlinson and team could never have imagined the volume we see today. The business world accounts for more than 108.7 billion emails sent and received per day, according to market researcher Radicati Group. That number is expected to increase to 139.4 billion by 2018. What makes email so useful—its ability to work across various devices and integrate different services—is also its greatest challenge.

Like his peers, Butterfield aims to weaken email’s iron grip by focusing on certain use cases. Internal work communication should be moved away from the classic in-box, he maintains, leaving email only for communication outside the workplace. The type of conversations that occur in advance of a product launch, for example, should be placed in an environment where people from different internal teams can easily see and respond to it.

And what about email exchanged with people beyond corporate walls? Yammer founder David Sacks, now COO of Zenefits, says some of the tasks for which people use email are moving to other apps. We no longer primarily use email to share photos and personal news; that’s what Facebook is for. We now send files with services such as Dropbox and Box. The best way to fix email may be to let it shrink back to its first role: digital mailbox rather than catchall communications hub.

Javier Soltero, general manager for Microsoft Outlook, doesn’t want to get rid of the in-box at all—just to make it more intuitive. Soltero, who late last year sold his intelligent email app, Acompli, to Microsoft for $200 million, believes that email is never going away. “Email is woven into the fabric of the Internet,” he says. “This is an accumulation problem.” His solution? A smarter in-box that can recognize frequent contacts and present messages from them more prominently.

Microsoft isn’t the only company working on in-box prioritization. Dropbox’s Mailbox quickly rose to prominence for its one-touch approach; Google’s GOOG Inbox soon followed by rethinking how Gmail items should be grouped. But each message still requires interaction, however small, leaving the core issue unaddressed.

What if technologists could apply artificial intelligence to the problem? Forty-four years after programmers sent the first email, a team of talented engineers is working on just that. X.ai, a startup in New York City, is experimenting with a personal assistant called Amy to schedule meetings for clients. Copying Amy on an email—as you would with a living, breathing assistant—prompts her to check your calendar for availability and negotiate a time and place. Founder Dennis Mortensen claims Amy is accurate 98% of the time for simple tasks.

The best way to address the email problem, it seems, is to cut out the human. Which, come to think of it, may have been the answer all along. 

How email senders are improving

Marketo — The San Francisco marketing-automation company believes that focus is the future. “Delivering the right message at the right time on the right channel makes all the difference,” says CMO Sanjay Dholakia. “That is what is driving revenue.”

Mailchimp — This Atlanta company’s mantra? “A purchased list is a dead list.” Translation: Don’t send to unwilling recipients. “Positive engagement falls off a cliff,” the company warned in a 2014 blog post. “The only thing that does go up? Complaints.”

Constant contact — Email should be optimized for the medium. Today it’s the mobile device. “Your emails are competing directly with all the other messages people receive,” says SVP Christopher Lister. So make them easy to read. —Kia Kokalitcheva

This story is from the May 1, 2015 issue of Fortune magazine.