In physicochemical treatments of biomolecular solutions, Gibbs energies are commonly encountered in two different forms. On the one hand, the macroscopic Gibbs energy serves as an indicator of equilibrium and spontaneous change in bulk samples. Specifically, thermodynamics defines this Gibbs energy such that it assumes a minimal value when an isothermal–isobaric system reaches equilibrium. On the other hand, the microscopic Gibbs energy serves as an indicator of the equilibrium distribution of biomolecules along a conformational coordinate or as a function of some other variable that serves to specify the state of the biomolecule. This Gibbs energy emerges from statistical mechanics, where it is introduced in such a way as to help reduce the enormous complexity inherent in a complete coverage of configuration space. Although the two kinds of Gibbs energies are, of course, two sides of the same coin, connecting them to one another in an explicit, quantitative manner is often perceived as challenging. This chapter first discusses two simple examples that show how biomolecular solutions may be viewed from either a macroscopic, thermodynamic standpoint or from a microscopic, statistical mechanical perspective. After reviewing the essential foundations of both approaches, it is exemplified how the minimisation of the macroscopic Gibbs energy commanded by the Second Law of Thermodynamics directly follows from proper integration of the microscopic Gibbs energy over the entire conformational space of a simple toy biopolymer.