The conventional approach for designing vaccine against a particular disease involves stimulation of the immune system using the whole pathogen responsible for the disease. In the post-genomic era, a major challenge is to identify antigenic regions or epitopes that can stimulate different arms of the immune system. In the past two decades, numerous methods and databases have been developed for designing vaccine or immunotherapy against various pathogen-causing diseases. This review describes various computational resources important for designing subunit vaccines or epitope-based immunotherapy. First, different immunological databases are described that maintain epitopes, antigens and vaccine targets. This is followed by in silico tools used for predicting linear and conformational B-cell epitopes required for activating humoral immunity. Finally, information on T-cell epitope prediction methods is provided that includes indirect methods like prediction of Major Histocompatibility Complex and transporter-associated protein binders. Different studies for validating the predicted epitopes are also examined critically. This review enlists novel in silico resources and tools available for predicting humoral and cell-mediated immune potential. These predicted epitopes could be used for designing epitope-based vaccines or immunotherapy as they may activate the adaptive immunity. Authors emphasized the need to develop tools for the prediction of adjuvants to activate innate and adaptive immune system simultaneously. In addition, attention has also been given to novel prediction methods to predict general therapeutic properties of peptides like half-life, cytotoxicity and immune toxicity.