Even with the emerging of newly-developed bone substitutes, poly(methyl methacrylate) (PMMA) cement is still a widely-used bone replacing biomaterial in orthopedic surgery with a long history. However, aseptic loosening, infection of the prosthesis and thermal necrosis to surrounding tissue are the common complications of PMMA. Therefore, additives have been incorporated in PMMA cement to target those problems. This chapter summarizes different additives to improve the performance of the PMMA cement, i.e.: (1) bioceramic additives; (2) filler additives; (3) antibacterial additives; (4) porogens; (5) biological agents, and (6) mixed additives. To improve the biological and mechanical performance of PMMA cement, mixed additives aiming to fabricate multifunctional PMMA seem the most suitable choice. Although in vivo animal studies have been conducted, long-term and clinical studies are still needed to evaluate the modifications of multifunctional PMMA cement for matching a specific clinical application.