Molecular-targeting therapy using tyrosine kinase inhibitor imatinib mesylate is effective for metastasis/recurrent gastrointestinal stromal tumors (GISTs). Likewise, imatinib would be effective in the neoadjuvant therapy for high-risk GIST. Neoadjuvant therapy may have the potential to increase the complete resection rate and to avoid the surgical rupture by decreasing the tumor size. Thereby, it is expected that improvement of recurrence rate and survival rate can be obtained by neoadjuvant therapy. Neoadjuvant therapy is also expected to be favored from the viewpoint of organ/function preservation by tumor shrinkage. The existing results of clinical trials established the feasibility of neoadjuvant imatinib therapy. However, proof of the survival effectiveness of neoadjuvant imatinib therapy has not been sufficiently demonstrated. The aim of this article is to introduce previous evidence and strategies regarding neoadjuvant therapy for GIST.