It is well known that alterations in the expression of the major sperm nuclear proteins (protamines) are related to infertility in man. In addition, other minor proteins extracted from human spermatozoa are being analysed by 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and identified by MALDI-TOF MS analysis. The function of the identified proteins turns out to be energy production, transcription, protein synthesis, transport, folding and turnover, cell cycle, apoptosis and oxidative stress, signal transduction, cytoskeleton, flagella and cell movement, cell recognition, metabolism and unknown function. Many of the proteins identified using MALDI-TOF had not been yet been described as being expressed in human spermatozoa. Substantial differences have been detected in the levels of some of the newly identified human sperm proteins in the different groups of infertile patients. Present research efforts are targeting the potential correlations among changes in the proteomic composition, protamine content, DNA integrity and assisted reproduction outcome.