Protein sequence motifs are signatures of protein families and can often be used as tools for the prediction of protein function. The generalization and modification of already known motifs are becoming major trends in the literature, even though new motifs are still being discovered at an approximately linear rate. The emphasis of motif analysis appears to be shifting from metabolic enzymes, in which motifs are associated with catalytic functions and thus often readily recognizable, to structural and regulatory proteins, which contain more divergent motifs. The consideration of structural information increasingly contributes to the identification of motifs and their sensitivity. Genome sequencing provides the basis for a systematic analysis of all motifs that are present in a particular organism. A systematically derived motif database is therefore feasible, allowing the classification of the majority of the newly appearing protein sequences into known families.