Over the last decades there has been a tremendous volume of research efforts focused on engineering silver-based (nano)materials. The interest in silver has been mostly driven by the element capacity to kill pathogenic bacteria. In this context, the main area of application has been medical devices that are at significant risk of becoming colonized by bacteria and subsequently infected. However, silver nanomaterials have been incorporated in a number of other commercial products which may or may not benefit from antibacterial protection. The rapid expansion of such products raises important questions about a possible adverse influence on human health. This review focuses on examining currently available literature and summarizing the current state of knowledge of the impact of silver (nano)materials on the immune system. The review also looks at various surface modification strategies used to generate silver-based nanomaterials and the immunomodulatory potential of these materials. It also highlights the immune response triggered by various silver-coated implantable devices and provides guidance and perspective towards engineering silver nanomaterials for modulating immunological consequences.