Optic neuritis (ON), an inflammatory optic neuropathy, is among the most common causes of visual loss. In its initial clinical appearance, ON may have unilateral or bilateral presentation, and anterior (papillitis) or retrobulbar localization. Traditionally, cases are divided into typical and atypical ON. In the Western hemisphere, most typical cases of optic nerve inflammation are associated with multiple sclerosis (MS). However, ON may also be associated with a series of disorders of known or initially undetected origin. Atypical ON has a somewhat different clinical picture from typical ON, and encompasses neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic recurrent neuroretinitis (NR), chronic relapsing inflammatory ON (CRION), ON within systemic autoimmune diseases, paraneoplastic and neuritis during or after infectious diseases or vaccination. The causes should be meticulously worked up, to address the therapeutic and prognostic challenges posed by these conditions. Here, we provide a brief overview of atypical ON, as encountered in our clinical practice, and additionally discuss the possible occurrence of optic neuropathies other than inflammatory and other ocular diseases within these disorders.