Macromolecules are essential cellular components in biological systems responsible for performing a large number of functions that are necessary for growth and perseverance of living organisms. Proteins, lipids and carbohydrates are three major classes of biological macromolecules. To predict the structure, function, and behaviour of any cluster of macromolecules, it is necessary to understand the interaction between them and other components through basic principles of chemistry and physics. An important number of macromolecules are present in mixtures with surfactants, where a combination of hydrophobic and electrostatic interactions is responsible for the specific properties of any solution. It has been demonstrated that surfactants can help the formation of helices in some proteins thereby promoting protein structure formation. On the other hand, there is extensive research towards the use of surfactants to solubilize drugs and pharmaceuticals; therefore, it is evident that the interaction between surfactants with macromolecules is important for many applications which includes environmental processes and the pharmaceutical industry. In this review, we describe the properties of different types of surfactants that are relevant for their physicochemical interactions with biological macromolecules, from macromolecules–surfactant complexes to hydrophobic and electrostatic interactions.