Phenotypic plasticity is the development of different phenotypes from a single genotype, depending on the environment. Such plasticity is a pervasive feature of life, is observed for various traits and is often argued to be the result of natural selection. A thorough study of phenotypic plasticity should thus include an ecological and an evolutionary perspective. Recent advances in large-scale gene expression technology make it possible to also study plasticity from a molecular perspective, and the addition of these data will help answer long-standing questions about this widespread phenomenon. In this review, we present examples of integrative studies that illustrate the molecular and cellular mechanisms underlying plastic traits, and show how new techniques will grow in importance in the study of these plastic molecular processes. These techniques include: (i) heterologous hybridization to DNA microarrays; (ii) next generation sequencing technologies applied to transcriptomics; (iii) techniques for studying the function of noncoding small RNAs; and (iv) proteomic tools. We also present recent studies on genetic model systems that uncover how environmental cues triggering different plastic responses are sensed and integrated by the organism. Finally, we describe recent work on changes in gene expression in response to an environmental cue that persist after the cue is removed. Such long-term responses are made possible by epigenetic molecular mechanisms, including DNA methylation. The results of these current studies help us outline future avenues for the study of plasticity.