ZBrush is the industry standard for digital sculpting and painting. It has a comprehensive toolset that allows for everything from 2D and 2.5D painting, to 3D sculpting and realistic rendering.
And it provides the most bang for the buck! Pixologic releases several revisions a year, and each have huge improvements as well as major new features, instead of just small bug fixes. And it interacts seamlessly with all major 3D applications.
Check out a few of the features of the latest version.