Neurological diseases are common and display symptomology that can significantly impact the quality of life for those diagnosed. As the brain controls many physiological functions, when neurological disorders develop and progress, comorbid conditions often occur. This progression is likely due to disease-associated changes in signaling pathways between the brain and downstream physiological processes. In this regard, hypothalamic-pituitary endocrine axes are highly vulnerable to becoming disrupted by neurological disorders. Disruptions in these pathways are of particular interest given their ability to drive feedback effects onto the brain, potentially exacerbating neurological symptoms and sustaining further endocrine disruption. Although some drugs, such as anti-seizure medications (ASMs), have been associated with promoting hypothalamic-pituitary dysfunction, there is also evidence that the neurological diseases themselves have the potential to generate and/or sustain comorbid hypothalamic-pituitary dysfunction due to the neuropathology of the diseases. Determining the mechanisms that connect neurological diseases to hypothalamic-pituitary dysfunction would foster the development of treatment options to alleviate the development of comorbidities, and potentially mitigate further disease propagation. In this review, we will present common neurological diseases that interact with and cause dysregulation of hypothalamic-pituitary components, with particular focus on epilepsy, and discuss how insights gleaned from clinical and pre-clinical epilepsy research of the last several decades can be applied to future studies investigating such disorders.