Know any tough, painful, lucrative problems?

I want to help people solve tough problems. Or, as Paul Graham calls them, schleps. Excerpt:

The most striking example I know of schlep blindness is Stripe, or rather Stripe's idea. For over a decade, every hacker who'd ever had to process payments online knew how painful the experience was. Thousands of people must have known about this problem. And yet when they started startups, they decided to build recipe sites, or aggregators for local events. Why? Why work on problems few care much about and no one will pay for, when you could fix one of the most important components of the world's infrastructure? Because schlep blindness prevented people from even considering the idea of fixing payments.

Have you experienced any personally or know of anyone who has? Big or small.