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 (inherited) or secondary (due to surgery, infection, or trauma). It often presents with chronic, progressive swelling.
Venous Insufficiency: A condition where the veins have problems returning blood from the legs back to the heart due to valve issues, leading to swelling, varicose veins, and skin changes.

Compartment Syndrome: A serious condition resulting from increased pressure within a muscle compartment, which can lead to muscle and nerve damage. It's characterized by severe pain, especially on palpation, and can be a medical emergency.
Phlegmasia Cerulea Dolens: A severe form of DVT that causes significant swelling and cyanosis of the affected limb, which can rapidly progress to gangrene if not promptly treated.
Ruptured Baker's Cyst: Although less common, a ruptured Baker's cyst can cause acute calf swelling and mimic other conditions like DVT, making it crucial to differentiate for appropriate management.

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 involve the feet.
Filarial Lymphedema (Elephantiasis): Caused by parasitic infections, this condition leads to severe, chronic swelling 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 skin discoloration. It's a rare condition that may be diagnosed at birth or later in life.