New mass spectrometry (MS) methods, collectively known as data independent analysis and hyper reaction monitoring, have recently emerged. These methods hold promises to address the shortcomings of data-dependent analysis and selected reaction monitoring (SRM) employed in shotgun and targeted proteomics, respectively. They allow MS analyses of all species in a complex sample indiscriminately, or permit SRM-like experiments conducted with full high-resolution product ion spectra, potentially leading to higher sequence coverage or analytical selectivity. These methods include MS(E), all-ion fragmentation, Fourier transform-all reaction monitoring, SWATH Acquisition, multiplexed MS/MS, pseudo-SRM (pSRM) and parallel reaction monitoring (PRM). In this review, the strengths and pitfalls of these methods are discussed and illustrated with examples. In essence, the suitability of the use of each method is contingent on the biological questions posed. Although these methods do not fundamentally change the shape of proteomics, they are useful additional tools that should expedite biological discoveries.