Corneal perforations in eyes with dry eye disease (DED) are difficult to manage due to the interplay of several factors such as the unstable tear film, surface inflammation, and the underlying systemic disease affecting the wound healing process, and the eventual outcome. A careful preoperative examination is required to identify the underlying pathology, and status of ocular surface and adnexa, rule out microbial keratitis, and order appropriate systemic workup in addition to assessing the perforation itself. Several surgical options are available, which include tissue adhesives, multilayered amniotic membrane grafting (AMT), tenon patch graft (TPG), corneal patch graft (CPG), and penetrating keratoplasty (PK). The choice of procedure depends upon the size, location, and configuration of the perforation. In eyes with smaller perforations, tissue adhesives are effective treatment modalities, whereas AMT, TPG, and CPG are viable options in moderate-sized perforations. AMT and TPG are also preferable in cases where the placement of a bandage contact lens may be a challenge. Large perforations require a PK, with additional procedures such as tarsorrhaphy to protect the eyes from the associated epithelial healing issues. Conjunctival flaps are considered in eyes with poor visual potential. The management of the acute condition is carried out in conjunction with measures to improve the tear volume bearing in mind the chances of delayed epithelialization and re-perforation in these cases. Administration of topical and systemic immunosuppression, when indicated, helps improve the outcome. This review aims to facilitate clinicians in instituting a synchronized multifaceted therapy for the successful management of corneal perforations in the setting of DED.