The generation of functional artificial lymphoid tissue will be a major focus of future research. In humans, this will be an alternative tool which induces specific immune responses at ectopic sites and offers a novel way to restore the immune status and to treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection, and immunodeficiency caused by primary defect or aging. Artificially synthesized lymphoid tissue may also provide us with a highly informative method to further study development and physiological functions of lymphoid tissues and organs. We recently reported successful generation of artificial lymph node-like tissues at ectopic sites in mouse. They showed a remarkable ability to induce secondary immune responses upon antigen stimulation, especially when transplanted into naïve or immunodeficient hosts. In this review, before discussing generation of synthetic immune systems, we first summarize previous knowledge on lymphoid development, which provides information valuable for making artificial lymphoid tissues such as spleen and lymph nodes. Then, we discuss problems that need to be solved in order to synthesize artificial lymphoid tissues, including several issues such as combinations of stromal cells, their cell types, soluble factors, and scaffold properties that enable proper accumulation and organization of immune cells in grafts.