Long-acting injectable (LAI) medications represent the combination of a powerful drug substance and an injectable drug formulation that guarantees that the affected tissue is consistently exposed to the active molecule for an extended therapeutic treatment period without eliciting unwanted side effects. Many marketed LAI drugs owe their success to a formulation principle that is perfectly tailored to the drug substance, yet to date there is no comprehensive overview of how drug molecules can be designed in a smart way to facilitate and accelerate technical formulation development at a later stage. This chapter summarizes the key properties of low-molecular weight drugs that are predestinated for different LAI formulations and suggests design principles as well as operational flow chart elements to streamline preclinical research and development at the interface of chemical and pharmaceutical sciences.