Syntactic foams are particulate polymer matrix composite materials consisting of hollow microspheres dispersed in a matrix. The matrix used in syntactic foams can be polymer, metal, or ceramic. Polymer matrices, particularly the thermosetting polymers, have been the most widely accepted matrices in syntactic foams. From the processing and application point of view, thermosetting syntactic foams have many advantages compared to thermoplastic ones. This chapter deals with syntactic foams based on various thermosetting resins and the chemistry of the resin systems. The resin systems are mainly phenolic, epoxy, cyanate ester, siloxane, polybenzoxazine, bismaleimide, and their blends. Apart from a brief chemistry of the parent resin systems, their syntactic foams have been described in detail. The aspects discussed are their processing, physical, thermal, and mechanical properties, applications, and degradation. Their properties can be engineered by a choice of matrix, microcell structure and its concentration, reinforcement, toughners, etc. While the thermal and thermo-physical characteristics are dictated by resin, mechanical and fracture characteristics are decided by both components. While epoxy, cyanate ester, and other such compounds provide structural syntactic foams, phenolics and their new generation versions provide thermo-structural materials. Syntactic foam ablators have made possible interplanetary space missions. Novel engineering concepts like lightweight self-healing give scope for extended applications of these systems. The recent advances in these areas are also discussed. These special materials with high specific strength are slated to replace conventional structural and thermo-structural materials in related engineering applications ranging from domestic to aerospace and defense.