薛雪与叶天士同乡同时代，相传二人曾因学术见解不同而互不相服，晚年方彼此推重（此说流传甚广，但细节多见于笔记小说，正史记载有限）。他精研湿热病证，撰成《湿热条辨》，系统辨析湿热病由表入里、上下三焦的传变规律及治法，与叶天士温热病理论互为补充，后世将他列为「温病四大家」之一。薛雪亦通诗文书画，非专职医者，行医被视为其余事。

Xue Xue was a contemporary and fellow townsman of Ye Tianshi; a widely circulated (though only loosely documented) anecdote holds that the two initially disagreed sharply on medical theory before coming to mutual respect later in life. He specialized in damp-heat pattern disease and wrote the Systematic Differentiation of Damp-Heat Disease, mapping how damp-heat conditions progress through the body and outlining corresponding treatments — complementing Ye Tianshi's warm-heat theory and earning him a place among the Four Great Masters of Warm Disease. Xue was also accomplished in poetry, calligraphy, and painting, and treated medicine as a secondary pursuit rather than a full-time vocation.