Advances in reproductive medicine have significantly increased the success of fertility treatments. Nevertheless, some women experience recurrent implantation failure (RIF) after in-vitro fertilization (IVF) or recurrent pregnancy loss (RPL). Imbalances in the immune system and failure to achieve immune tolerance to the foetus have been implicated as potentially modifiable causes of idiopathic RIF and RPL. As such, women are increasingly being treated with immunomodulatory agents in an attempt to achieve a successful pregnancy. This systematic review examines the published evidence on immune changes in these patients, the use of immunomodulation therapies and diagnostic testing modalities to guide their use or to identify patient subsets most likely to benefit. The PubMed database was searched for the terms “recurrent implantation failure” and “recurrent pregnancy loss” in conjunction with T-helper (Th) cells and their subsets in particular; Th1, Th2, Th17 and T-regulatory (Treg) cells, natural killer (NK) cells, cytokine imbalance as well as immune modulators and immune suppressants. The reference lists of articles were examined to identify additional articles. There remains limited data on the immunological changes in cytokine and cellular profiles during the hormonal cycle as well as prior to, during and after implantation in health as well as idiopathic RIF and RPL. There is a need to advance immunological diagnostics to match the clinical need in this emerging field and to guide clinicians to make optimal and safe therapeutic choices. It is also imperative that the well-being of the infants conceived after such intervention is monitored.