Number theory is known to be a field in which many questions that can be understood by secondary-school pupils have defied the most formidable mathematicians' attempts to answer them.
Calculus is not known to be such a field, as far as I know. (For now, let's just assume this means the basic topics included in the staid and stagnant conventional first-year calculus course.)
What are
- the most prominent and
- the most readily comprehensible
questions that can be understood by those who know the concepts taught in first-year calculus and whose solutions are unknown?
I'm not looking for problems that people who know only first-year calculus can solve, but only for questions that they can understand. It would be acceptable to include questions that can be understood only in a somewhat less than logically rigorous way by students at that level.

Many indefinite integrals fit this, the poster child being $\int \exp(-x^2)\,dx$ Easy to ask, hard to answer (unless you count the error function as an answer, but in this case that sounds like giving a name to the unknowable).