Gastrointestinal (GI) perforations are rare events in rheumatoid arthritis (RA) patients, but cause significant morbidity and mortality. Several studies indicate that RA patients may be at higher risk of GI perforation. Traditional RA treatments such as glucocorticoids and non-steroidal anti-inflammatory drugs increase the risk of perforation. In the past two decades, a new class of therapeutic agents called biologics has been added to the RA treatment armamentarium. Biologics are effective in controlling disease activity and are generally well tolerated; however, reports of GI perforations in association with biologics have arisen. In particular, drugs that inhibit the interleukin (IL)-6 cytokine receptor have demonstrated a higher risk of perforation compared with other therapies. Recent reports also suggest that janus kinase inhibitors may increase the risk of perforation, perhaps via downstream effects on IL-6 signaling. In this review, we discuss current data on the risk of GI perforations among RA patients receiving targeted therapies and its clinical relevance.