The article reviews the effects of macromolecular crowding and confinement on biochemical and biophysical processes, focusing on the changes in free energy, reaction rates, and equilibria. It discusses the theoretical and experimental literature published from 2004 onwards, highlighting the impact of excluded volume interactions on various macromolecular reactions. The authors classify the effects of crowding and confinement into three prototypical reactions: bimolecular association, site binding, and protein folding. They use thermodynamic models to predict the effects of these interactions and compare them with experimental data. The review also addresses the complexity introduced by the heterogeneity of local environments and nonspecific interactions in biological media. The authors suggest theoretical and experimental approaches to better understand the effects of crowding and confinement in living organisms, emphasizing the need for a "bottom-up" approach to model increasingly complex systems.The article reviews the effects of macromolecular crowding and confinement on biochemical and biophysical processes, focusing on the changes in free energy, reaction rates, and equilibria. It discusses the theoretical and experimental literature published from 2004 onwards, highlighting the impact of excluded volume interactions on various macromolecular reactions. The authors classify the effects of crowding and confinement into three prototypical reactions: bimolecular association, site binding, and protein folding. They use thermodynamic models to predict the effects of these interactions and compare them with experimental data. The review also addresses the complexity introduced by the heterogeneity of local environments and nonspecific interactions in biological media. The authors suggest theoretical and experimental approaches to better understand the effects of crowding and confinement in living organisms, emphasizing the need for a "bottom-up" approach to model increasingly complex systems.