Simulations of crystallization from solution are typically carried out in the canonical or isothermal-isobaric ensembles, where the total number of atoms/molecules is constant. When dealing with out-of-equilibrium, multicomponent liquid phases undergoing a phase transition, this constraint introduces a coupling between the number of solute monomers available to a growing crystal nucleus and the time-dependent crystallization driving force, Δ𝜇 𝓁→𝑥𝑡𝑎𝑙 . Indeed, nucleation can be completely inhibited in a microscopic, closed system, if the transfer of monomers from the liquid to a critical cluster of the new phase renders the solution undersaturated. In a dense system, such as a liquid solution, this coupling cannot be efficiently removed by simulating in the grand canonical ensemble (where the solute is replenished from an artificial, external reservoir to maintain a constant solution chemical potential), due to a low probability for insertion of solute in the liquid phase. Instead, molecular simulations using a constant number of molecules require either the application of theoretical corrections to account for the change in Δ𝜇 𝓁→𝑥𝑡𝑎𝑙 or the development of specialised methods to mimic open boundary conditions, unless sufficiently large systems can be simulated to minimise the finite-size effects.