Bone tissue engineering based on scaffolds is quite a complex process as a whole gamut of criteria needs to be satisfied to promote cellular attachment, proliferation and differentiation: biocompatibility, right surface properties, adequate mechanical performance, controlled bioresorbability, osteoconductivity, angiogenic cues, and vascularization. Third generation scaffolds are more of composite types to maximize biological-mechanical-chemical properties. In the present review, our focus is on the performance of microorganism-derived polyhydroxyalkanoates (PHAs)-polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-valerate (PHBV)-composite scaffolds with ceramics and natural polymers for tissue engineering applications with emphasis on bone tissue. We particularly emphasize on how material properties of the composites affect scaffold performance. PHA-based composites have demonstrated their biocompatibility with a range of tissues and their capacity to induce osteogenesis due to their piezoelectric properties. Electrospun PHB/PHBV fiber mesh in combination with human adipose tissue-derived stem cells (hASCs) were shown to improve vascularization in engineered bone tissues. For nerve and skin tissue engineering applications, natural polymers such as collagen and chitosan remain the gold standard but there is scope for development of scaffolds combining PHAs with other natural polymers which can address some of the limitations such as brittleness, lack of bioactivity and slow degradation rate presented by the latter. (C) 2016 Wiley Periodicals, Inc.