Responsive design is a hot topic of web development these days, and with a simple (and now well supported) way of handling the ‘one site for all clients’ model (and I mean clients as in browsers/platforms/devices, not the people that give you money in return for a web site) it should well be.
Using collections of utilities, such as the excellent 320&up, makes building responsively much easier, and handles most of the gotchas for you automatically, so instead of fretting on the technical side of implementing a responsive build, the challenge now rests on the responsive design and User Experience of the site, I.E. how should these content regions stack up in a mobile view? What is the best way to show this sidebar in a single-column layout? Building it is easy; thinking about how the design should adapt itself is the tricky part.