Drugs exert their functions mainly by affecting proteins. Therefore, it seems straightforward to focus on proteins in order to investigate drug effects. Unfortunately, proteins are of very high complexity, rendering it much more difficult to screen for protein alterations as compared to gene regulation. However, the efficiency and applicability of proteome analysis has been dramatically increased recently. We are on the way to be able to comprehensively assess disease-related proteome alterations, which may become an essential source of information for knowledge-based drug design. This review will provide an overview of current techniques in proteome analysis, focusing on screening technologies for biomedical research. An outlook at the future potential of proteomics supported by modern bioinformatics will highlight why proteomics is worth the effort.