Crystalline porous materials are extremely important for developing catalytic systems with high scientific and industrial impact. Metal–organic frameworks (MOFs) show unique potential that still has to be fully exploited. This perspective summarizes the properties of MOFs with the aim to understand what are possible approaches to catalysis with these materials. We categorize three classes of MOF catalysts: (1) those with active site on the framework, (2) those with encapsulated active species, and (3) those with active sites attached through post-synthetic modification. We identify the tunable porosity, the ability to fine tune the structure of the active site and its environment, the presence of multiple active sites, and the opportunity to synthesize structures in which key–lock bonding of substrates occurs as the characteristics that distinguish MOFs from other materials. We experience a unique opportunity to imagine and design heterogeneous catalysts, which might catalyze reactions previously thought impossible.