Summary. This chapter presents a broad overview of Computational Intelligence (CI) techniques including Artificial Neural Networks (ANN), Particle Swarm Optimization (PSO), Genetic Algorithms (GA), Fuzzy Sets (FS), and Rough Sets (RS). We review a number of applications of computational intelligence to problems in bioinformatics and computational biology, including gene expression, gene selection, cancer classification, protein function prediction, multiple sequence alignment, and DNA fragment assembly. We discuss some representative methods to provide inspiring examples to illustrate how CI could be applied to solve bioinformatic problems and how bioinformatics could be analyzed, processed, and characterized by computational intelligence. Challenges to be addressed and future directions of research are presented. An extensive bibliography is also included.