This review discusses the structural and functional diversity of protein–protein interactions (PPIs), focusing on protein families with known three-dimensional structures. PPIs play diverse roles in biology, differing in composition, affinity, and whether the association is permanent or transient. In vivo, the localization, concentration, and environment of protomers influence interaction and complex composition. Transient PPIs are crucial for biological regulation. The review explores different types of PPIs, including homo- and hetero-oligomeric complexes, obligate and non-obligate interactions, and transient versus permanent complexes. It highlights how structural characteristics relate to physiological function, specificity, and evolution. PPIs can be controlled by factors such as local concentration, physicochemical environment, and molecular triggers. Structural data reveals that obligate complexes often have larger, more hydrophobic interfaces, while non-obligate interactions may have more polar interfaces. The review also discusses the evolution of PPIs, noting that their structure and affinity are tuned to biological function and physiological conditions. Variations in oligomeric states within homologous protein families reflect adaptation to different functions and environments. The review concludes that PPIs are highly diverse, with many complexes involving transient interactions, and that understanding their structure, function, and evolution is crucial for predicting and modeling their behavior.This review discusses the structural and functional diversity of protein–protein interactions (PPIs), focusing on protein families with known three-dimensional structures. PPIs play diverse roles in biology, differing in composition, affinity, and whether the association is permanent or transient. In vivo, the localization, concentration, and environment of protomers influence interaction and complex composition. Transient PPIs are crucial for biological regulation. The review explores different types of PPIs, including homo- and hetero-oligomeric complexes, obligate and non-obligate interactions, and transient versus permanent complexes. It highlights how structural characteristics relate to physiological function, specificity, and evolution. PPIs can be controlled by factors such as local concentration, physicochemical environment, and molecular triggers. Structural data reveals that obligate complexes often have larger, more hydrophobic interfaces, while non-obligate interactions may have more polar interfaces. The review also discusses the evolution of PPIs, noting that their structure and affinity are tuned to biological function and physiological conditions. Variations in oligomeric states within homologous protein families reflect adaptation to different functions and environments. The review concludes that PPIs are highly diverse, with many complexes involving transient interactions, and that understanding their structure, function, and evolution is crucial for predicting and modeling their behavior.