Deep Vein Thrombosis (DVT): This is often the first consideration for unilateral leg swelling due to its relatively high prevalence and potential for serious complications, such as pulmonary embolism. Risk factors include recent surgery, immobilization, cancer, and genetic predispositions to clotting.

Cellulitis: A bacterial infection of the skin and subcutaneous tissues, which can cause swelling, redness, warmth, and pain in one leg. It's more common in individuals with compromised immune systems or those with a history of trauma to the affected area.
Lymphedema: Swelling caused by impaired lymph drainage, which can be primary (genetic) or secondary (due to surgery, infection, or trauma). It often presents with non-pitting edema and can be unilateral.
Venous Insufficiency: Includes conditions like varicose veins and chronic venous hypertension, leading to swelling, usually more pronounced at the end of the day and alleviated by elevation.

Compartment Syndrome: A medical emergency characterized by increased pressure within a muscle compartment, leading to pain, swelling, and potentially permanent damage if not promptly treated. It often occurs after trauma or intense exercise.
Arterial Occlusion: Sudden blockage of an artery, which can cause severe pain, pallor, pulselessness, poikilothermia, paresthesias, and paralysis (the "6 Ps"). It's a medical emergency requiring immediate intervention.
Necrotizing Fasciitis: A severe infection of the fascia and tissues beneath the skin, which can rapidly progress and is life-threatening. It presents with severe pain out of proportion to the visible signs of infection.

Lipedema: A chronic condition characterized by the abnormal growth of fat cells in the legs, leading to swelling and pain. It's often mistaken for lymphedema but does not typically respond to elevation.
Filarial Elephantiasis: Caused by parasitic worms transmitted through mosquito bites, leading to severe swelling and disfigurement of the affected limb. It's rare in developed countries but should be considered in travelers or immigrants from endemic areas.
Klippel-Trenaunay Syndrome: A congenital condition involving vascular malformations, which can cause unilateral leg swelling, varicose veins, and port-wine stains. It's present at birth and can lead to chronic swelling and other complications.