Apoptosis or programmed cell death, is a part of the normal life cycle of many, perhaps all, cell types and has emerged as a very important regulatory pathway in oncogenesis and in the pathogenesis of many human diseases. Apoptosis is used for the systematic elimination of excess, damaged or hazardous somatic cells. It is a process by which the cell commits cellular suicide in a systematic, highly energy dependent method of disassembly and packaging. One potential strategy to improve adjuvant therapy in sarcomas is to induce programmed cell death or apoptosis in the tumor by administration of antisense phosphorothioate oligonucleotides (AS ODNs) or small interfering RNA (siRNA). Both are designed to target specific mRNA sequences thought to be involved in oncogenesis. For example, Oblimersen (G3139) is a phosphorothionate anti-Bcl-2 oligonucleotide that has proven to be both a theoretical and clinically relevant treatment modality in non-sarcomatous malignancies. The combination of G3139 with doxorubicin, has demonstrated increased antitumor activity. Synovial sarcoma is a particularly good candidate for this strategy because synovial sarcoma expresses high levels of Bcl-2, a critical negative regulator of apoptosis. Over-expression of Bcl-2 substantially prolongs cell survival when other apoptotic inducing factors are present. Increased Bcl-2 expression not only leads to the development of cancer but also to resistance of many anti-cancer chemotherapeutic agents. Because synovial sarcoma over-expresses Bcl-2 in over 90% of cases, inhibition of apoptosis is a potential mechanism by which synovial sarcoma may overwhelm its host leading to the death of the patient. Accordingly, inhibition of Bcl-2 expression may increase overall survival of individuals afflicted with synovial sarcoma.