A peptidomimetic macrocycle or a pharmaceutically acceptable salt thereof and at least one additional pharmaceutically active agent for use in the treatment of cancer in a subject in need thereof, wherein the peptidomimetic macrocycle or the pharmaceutically acceptable salt thereof antagonizes the activity of p53 and/or MDM2 and/or MDMX, and wherein the peptidomimetic macrocycle comprises an amino acid sequence which is at least 60% identical to an amino acid sequence in any of Table 1, Table 1a, Table 1b, and Table 1c, and wherein the peptidomimetic macrocycle has the formula: wherein: each A, C, D, and E is independently an amino acid; each B is independently an amino acid, [-NH-L 3 -CO-], [-NH-L 3 -SO 2 -], or [-NH-L 3 -]; each R 1 and R 2 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-; or forms a macrocycle-forming linker L' connected to the alpha position of one of said D or E amino acids; each R 3 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, aryl, or heteroaryl, optionally substituted with R 5; each L and L' is independently a macrocycle-forming linker of the formula -L 1 -L 2 -; each L 1, L 2, and L 3 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, or [-R 4 -K-R 4 -] n, each being optionally substituted with R 5; each R 4 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; each K is independently O, S, SO, SO 2, CO, CO 2, or CONR 3; each R 5 is independently halogen, alkyl, -OR 6, -N(R 6) 2, -SR 6, -SOR 6, -SO 2 R 6, - CO 2 R 6, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 6 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 7 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted with R 5, or part of a cyclic structure with a D residue; each R 8 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted with R 5, or part of a cyclic structure with an E residue; each v is independently an integer from 1-1000; each w is independently an integer from 3-1000; u is an integer from 1-10; each x, y and z is independently an integer from 0-10; and each n is independently an integer from 1-5; wherein the at least one additional pharmaceutically active agent is fulvestrant, everolimus, romidepsin, palbociclib, trametinib, rituximab, dabrafenib, vemurafenib, azacitidine, decitabine, midostaurin, vincristine, cyclophosphamide or cytarabine. each A, C, D, and E is independently an amino acid; each B is independently an amino acid, [-NH-L 3 -CO-], [-NH-L 3 -SO 2 -], or [-NH-L 3 -]; each R 1 and R 2 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-; or forms a macrocycle-forming linker L' connected to the alpha position of one of said D or E amino acids; each R 3 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, aryl, or heteroaryl, optionally substituted with R 5; each L and L' is independently a macrocycle-forming linker of the formula -L 1 -L 2 -; each L 1, L 2, and L 3 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene, or [-R 4 -K-R 4 -] n, each being optionally substituted with R 5; each R 4 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; each K is independently O, S, SO, SO 2, CO, CO 2, or CONR 3; each R 5 is independently halogen, alkyl, -OR 6, -N(R 6) 2, -SR 6, -SOR 6, -SO 2 R 6, - CO 2 R 6, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 6 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 7 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted with R 5, or part of a cyclic structure with a D residue; each R 8 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted with R 5, or part of a cyclic structure with an E residue; each v is independently an integer from 1-1000; each w is independently an integer from 3-1000; u is an integer from 1-10; each x, y and z is independently an integer from 0-10; and each n is independently an integer from 1-5;