I feel one of the most challenging issues is how each of us defines Bioinformatics/Computational Biology. It's such a broad term and our specific area of interest may not match with that of our PIs. And related to this is, what prerequisites to match, even when just expanding knowledge-base. I was trained to look for and use existing tools to help with my analysis. Right now, I need to learn programming to run codes for my analysis. Then comes the choice of programming language. While the concepts hold for all languages, it's usually best to master one over the others (or maybe all). But hey, that's what keeps us going, I guess -The cycle of learning and applying.. I'm still at the very start of my career, I am sure my response will change few years down the line. Looking to hear from others who have crosses this stage already.