How does novelty, a new, genetically based function, evolve? A compelling answer has been elusive because there are few model systems where both the genetic mechanisms generating novel functions and the ecological conditions that govern their origin and spread can be studied in detail. This review article considers what we have learned about the evolution of novelty from microbial selection experiments. This work reveals that the genetic routes to novelty can be more highly variable than standard models have led us to believe and underscores the importance of considering both genetics and ecology in this process.