Median arcuate ligament syndrome (MALS) is associated with several other complex chronic illnesses that may overlap and contribute to the worsening of MALS symptoms. Some of these comorbid conditions include postural orthostatic tachycardia syndrome (POTS), Ehlers Danlos syndrome (EDS), and mast cell activation syndrome (MCAS). The association between POTS, EDS, and MCAS has been relatively well established and together, are often referred to as the “trifecta.” There is emerging evidence that these conditions are also associated with MALS. In fact, they appear to be more prevalent in the MALS population (Huynh et al., Am Surg 85(10):1162–1165, 2019). In a survey of 242 patients in the abdominal vascular compression syndrome community groups for MALS, 53% of those who responded were found to have dysautonomia, 32% EDS, and 23% MCAS (Sturiale et al., Int J Surg Case Rep 4(4):399–402, 2013). All these rates are higher than the prevalence found in the general community, thus highlighting a possible underlying mechanism between MALS and each of these conditions. Unfortunately, there is still much heterogeneity in symptom presentation and lack of understanding around the underlying pathophysiology of all these conditions, making them difficult to treat. Some patients who elect to undergo a MALS operation continue to have symptoms if they also have these associated conditions (DeCicco et al., Surgery 175(3):822–832, 2024). This chapter aims to summarize the current understanding of these associated conditions and how they play into the development and presentation of MALS. We highlight specific symptoms and patterns surgeons should look for in a MALS evaluation and give treatment recommendations.