Kevin Systrom

You know what, the lowest point was the first day we launched Instagram. We had everything set up, all this press out, everyone looking at us, and our server immediately crashed because it was over capacity. I told myself that maybe we just blew our one chance at everyone being excited about us. Obviously, that wasn't the case.

Matt Cohler

The Facebook-Yahoo acquisition talks in 2006. Our growth had (temporarily!) stalled out, and for the first and only time, the way forward for Facebook was for a brief time unclear.

Binta Niambi Brown

I'd have to say for me, becoming suddenly ill in my early thirties was pretty difficult -- it was really hard for me to accept being so sick, so I pushed myself to go back to work way before I was ready, which jeopardized my health, but also, in some ways my career and therefore my ability to do good and to really make a difference in the world. So yeah, that was an exceptionally difficult time for me personally.

Aditya Ghosh

It was when I was a rookie lawyer about 11 years ago and an oversight of mine was nearly going to cost the client a few million dollars. But the low point was that I was trying to be a hero while working on the deal and didn't ask for help from my seniors when I knew I needed it.

Sal Khan

Getting yelled at within 2 weeks of starting a new consulting job when I was 22. It made me cry.

Jeff George

The lowest point in my career was probably midway through my first year at McKinsey & Co. as a new associate there. I was working 90-100 hours per week under a lot of pressure and I doubted myself a lot. Over a third of my incoming class had just been "counseled out" after the recessionary dip in the economy following 9/11, and as great an experience as I had at McKinsey overall, my first 6-9 months there were pretty miserable.

My second and third year at McKinsey were a lot better -- once I began managing people and working for people I really respected, I almost never worked on the weekends and didn't ask my team to either.

Ben Rattray

When we were struggling financially in our first year, I had to ask my youngest brother to loan me $3,000 to keep the company afloat. It was definitely a humbling experience and gave me new appreciation for my brother.

Eric Ryan

We went through a round of layoffs back in 2008 during the recession, which was by far the worst point of my career. Taking someone's job away -- especially after you have cultivated a culture of care and friendship -- was incredibly painful for everyone. I swore we would never relive that again, and ever since, we've been more conservative on staffing.

Brian Deese

July/August 2011 debt limit debate was a low point for Washington and economic policymaking in general.

Jennifer Carter Fleiss

Sleeping under my desk during a summer internship at an investment bank!

Brian Chesky

Starting Airbnb. It was exciting and in hindsight it's nostalgic and romantic but at the top it wasn't at all. It was actually very scary. And because it's so scary it seems nostalgic now -- but no one wanted to be back in those days.