As a result of the low oral bioavailability of several drugs, there is a renewed interest for parenteral administration to target their absorption directly into the blood bypassing the long gastrointestinal route and hepatic metabolism. In order to address the potential side effects of frequent injections, sustained release systems are the most popular approaches for achieving controlled long-acting drug delivery. Injectable in-situ forming implants (ISFIs) have gained greater popularity in comparison to other sustained systems. Their significant positive aspects are attributed to easier production, acceptable administration route, reduced dosing frequency and patient compliance achievement. ISFI systems, comprising biodegradable polymers such as poly (lactide-co-glycolide) (PLGA) based on solvent exchange mechanisms, are emerged as liquid formulations that develop solid or semisolid depots after injection and deliver drugs over extended periods. The drug release from ISFI systems is generally characterized by an initial burst during the matrix solidification, followed by diffusion processes and finally polymeric degradation and erosion. The choice of suitable solvent with satisfactory viscosity, miscibility and biocompatibility along with considerable PLGA hydrophobicity and molecular weights is fundamental for optimizing the drug release. This overview gives a particular emphasis on evaluations and the wide ranges of requirements needed to achieve reasonable physicochemical characteristics of ISFIs.