Since the introduction of the proteome term somewhat more than a decade ago the field of proteomics witnessed a rapid growth mainly fueled by instrumental analytical improvements. Of particular notice is the advent of a diverse set of gel-free proteomics techniques. In this review, we discuss several of these gel-free techniques both for monitoring protein concentration changes and protein modifications, in particular protein phosphorylation, glycosylation, and protein processing. Furthermore, different approaches for (multiplexed) gel-free proteome analysis are discussed.