Recent development and clinical application of novel anticancer agents like S-1 have been reported to show a good outcome against gastric cancer (GC) with peritoneal dissemination (P). In our study, a retrospective analysis of the treatment for GC with P was performed. Since 1989, a chemosensitivity test with MTT assay (MTTA) using surgical specimen was performed to choose chemotherapy after surgery, resulting in good prognosis in patients who received drugs which were determined effective by the MTTA. Since 1999, S-1 was introduced as adjuvant chemotherapy, and, since 2002, initial treatment with S-1/CDDP was used for GC with P, suggesting a better prognostic outcome compared with previous results with ineffective chemotherapy or surgery alone. In conclusion, prognosis of GC with P has been improving by effective regimens with novel anticancer agents like S-1. Further research and clinical trials will be necessary to achieve a more satisfactory outcome with the treatment of GC with P.