Microtubule-associated proteins (MAPs) function to regulate the assembly dynamics and organization of microtubule polymers. Upstream regulation of MAP activities is the major mechanism used by cells to modify and control microtubule assembly and organization. This review summarizes the functional activities of MAPs found in animal cells and discusses how these MAPs are regulated. Mechanisms controlling gene expression, isoform-specific expression, protein localization, phosphorylation, and degradation are discussed. Additional regulatory mechanisms include synergy or competition between MAPs and the activities of cofactors or binding partners. For each MAP it is likely that regulation in vivo reflects a composite of multiple regulatory mechanisms.