PUF proteins are RNA-binding proteins named for founding members PUMILIO and fem-3 binding factor (FBF). Together these proteins represent the range of known RNA recognition properties. PUMILIO is a prototypical PUF protein whose RNA sequence specificity is simple, elegant, and predictable. FBF displays differences in RNA recognition that represent divergence from the prototype. Here we review recent studies that examine the engineering of sequence specificity of PUF proteins and its applications as well as studies that increase our understanding of the natural diversity of RNA recognition by this family of proteins.