Mathematical modeling of gas-solid reactions is very common in chemical engineering, but liquid-solid reactions have received much less attention. Modeling of liquid-solid reactions is not studied very much, but it is gaining importance because the principles of chemical reaction engineering have made a breakthrough in industries dealing with fine and specialty chemicals. General principles for the modeling of complex organic liquid-solid reaction systems in backmixed batch and semibatch reactors are presented. The ingredients of the model are complex kinetics, interfacial mass transfer, and models for solid particles and the reactor. Previously developed theories for solid particles, such as shrinking-particle and porous-particle models, can be applied on liquid-solid systems, but the kinetics is complex and the reactions are carried out (semi)batchwise, which implies that numerical solution algorithms are used. The approach is illustrated with two experimental case studies representing shrinking and porous particles, Claisen condensation and carboxyalkylation of cellulose. Following the modeling principles, it was possible to describe the experimental data very well and predict the behavior of solid particles and the reactor performance. Detailed modeling of the liquid-solid reactions will be used extensively in process scale-up in the future.