In 1891, having decided to retire from composition, Brahms traveled to Meiningen, where he met the assistant conductor and principal clarinetist of the Meiningen Orchestra, Richard Mühlfeld. The clarinetist's performance of works by Weber and Mozart had a profound affect upon Brahms, who called him "the greatest wind player alive." He later wrote to Clara Schumann that "it is impossible to play the clarinet better than Herr Mühlfeld does here." Brahms observed Mühlfeld practicing and studied the capabilities of his instrument. The composer's rejuvenation bore fruit at once with the Trio, Op. 114, and the Quintet, Op. 115; soon after came Brahms' final instrumental compositions, the two clarinet Sonatas, Op. 120. The Quintet was performed by Mühlfeld, with the string quartet led by the violinist Joseph Joachim.

In his book on Brahms, Malcolm MacDonald has remarked perceptively that Brahms was struck by the "polish and feminine sensitivity" of Mühlfeld's playing: "and the works he wrote for him offer comparatively few opportunities for displays of vertiginous bravura, but continual ones for the exercise of refined musicality, intimate expression and beautiful tone."

The Clarinet Quintet is regarded by some critics as Brahms' most beautiful chamber work. The balance and integration of the clarinet and strings are remarkable. The Quintet is economical in its motives, relying on Brahms' technique of thematic transformation and variation, and it blends intense Romantic lyricism with mature introspection. Harmonies are rich, and the textures are lush. The first movement, which is in sonata form, opens with one of Brahms' most affecting main themes. The second movement is ternary. Its slow, main section is sweetly poignant and melancholy, while the middle section is a masterly evocation of gypsy music. The third movement begins like a somewhat slow intermezzo but then shifts to the faster and more scherzo-like main section of the movement. The theme of the scherzo-like section is derived from that of the initial section. This movement concludes with a brief allusion to its opening music. The finale is a theme and variations with a profoundly beautiful mood of meditative reflection. In the finale's coda, one of the most obvious unifying elements of this Quintet is the recollection of the main theme from the first movement.