Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens. In terms of T cell activation, although CD3 has been widely applied in bispecific scFvs being developed, CD28 and CD137 among co-stimulatory signals are also ideal candidates to be evaluated. Besides, LIGHT and HIV-Tat101 have drawn much attention as their potential roles in modulating antitumor responses.