The increasing popularity of gel-free proteomics technologies has created a strong demand Received: July 6, 2009 for compatible quantitative analysis methods. As a result, a plethora of different techniques Revised: October 6, 2009 has been proposed to perform gel-free quantitative analysis of proteomics samples. Each of Accepted: October 27, 2009 these methods comes with certain strengths and shortcomings, and they often are dedicated to a specific purpose. This review will present a brief overview of the main methods, organized by their underlying concepts, and will discuss the issues they raise with a focus on data processing. Finally, we will list the available software that can help with the data processing from quantitative experiments. We hope that this review will thus enable researchers to find the most appropriate method available for their research objectives, and can also serve as a basis for creating a reliable data processing strategy.