Small molecule drugs, compounds typically <1 kD in mass, comprise a large portion of the therapeutic market. These drugs usually operate by agonizing or antagonizing the active site on a disease-linked protein of interest, though allosteric regulation is possible. With an estimated 93% of the human proteome lacking druggable binding sites, methods have been developed to modulate protein activity through binding of any available site rather than only the active site. These drugs contain a target protein binding warhead in addition to a linker-separated active domain. This domain may recruit a second protein to the proximity, induce protease-mediated degradation, or recruit a kinase for directed phosphorylation, among other functions. These drugs expand both the mechanism of action for small molecule therapeutics and the pool of potential protein targets.