Figure 1. Distinct strategies for selective and unselective targeting of the mTOR complexes. Rapamycin and related rapalogues acutely target mTORC1 specifically, although chronic exposure can also limit mTORC2 function in a context specific manner. Alternatively, mTOR catalytic inhibitors do not discriminate between the complexes. Targeting complex-specific subunits provides an alternative route to specific blockade. mTORC2 complex disruption, either through genetic deletion of Rictor or with small molecules, leads to loss of the entire complex. Alternatively, disruption of substrate recruitment can uncouple mTORC2 from its targets, while leaving the complex intact. Contrasting these distinct approaches will help define therapeutic opportunities and liabilities associated with mTOR inhibition.