The generation of human induced pluripotent stem cells (iPSCs) from differentiated cells holds important clinical implications. Human iPSCs represent the most promising resource for regenerative medicine by enabling the use of patient-specific cells of any lineage without the need for embryonic material. However, before therapeutic applications using human iPSCs are carried out, extensive analyses are needed to assess molecular differences and similarities between human iPSCs and their natural counterparts, human embryonic stem cells. The pluralism of mechanisms acting in a biological system can be better approached by studying several elements simultaneously in an unbiased manner. This review will discuss recent genome-wide analyses of iPSCs (e.g., transcripts and epigenetics) and will introduce the huge potential of mass spectrometry-based proteomics in decoding the unique mechanisms underlying the reprogramming process and the molecular nature of cellular identity.