Short peptides are attractive building blocks for supramolecular biomaterials for their low-cost, scalability of production and purification, possibility to encode biological messages, and to be processed by enzymes to fine-tune their lifetime toward controlled biodegradation. Over the last few decades, great progress has been made in the understanding of these building blocks for their tailored design to a variety of biological applications. This chapter reviews the design strategies to achieve hydrogels that have been applied to address a variety of biomedical needs. As more knowledge has been gathered in the field, a higher complexity could be achieved, for instance to target subcellular organelles, specific cells, and even to stimulate the immune response. Overall, self-assembling short peptides are reaching their full potential and have opened the gates to new paradigms in therapy to realize futuristic medicine.