Cathepsin K is a cysteine protease that plays an important role in the pathological process of bone resorption. Selective cathepsin K inhibitors may thus provide great potential in the treatment of osteoporosis. Pharmaceutical interest in this area is highlighted by the rising number of publications and patent applications. Most recently, the interim results of three clinical trials conducted by Novartis, GlaxoSmithKline, and Merck have strengthened the validation of the target for the therapeutic intervention of osteoporosis. Here we report a series of Cbz-leucyl-(4-piperidinylphenyl)aminoethyl amides based on dipeptidyl anilines for cathepsin K inhibition. These new non-covalent inhibitors exhibit single digit nM inhibition of the cathepsin family. Molecular modeling studies on the interactions responsible for the potency of these inhibitors for cathepsin K will be also discussed.