One of the central themes in "Arthur Conan Doyle: A Life in Letters" is Conan Doyle's complex relationship with the success of Sherlock Holmes. While the character brought him fame and fortune, it also became a burden, overshadowing his other literary works and personal aspirations. The letters provide insight into his efforts to balance his creative ambitions with the demands of his most famous creation.

The book highlights Conan Doyle's journey from a humble country doctor to a renowned author and public figure. His correspondence reflects his evolving views on literature, his growing confidence as a writer, and his engagement with contemporary social and political issues. This theme underscores the dynamic nature of his career and the breadth of his intellectual pursuits.

Another significant theme is Conan Doyle's deep commitment to Spiritualism, particularly in his later years. The letters reveal his passionate advocacy for the movement, his personal experiences with the supernatural, and his efforts to promote Spiritualism despite widespread skepticism. This theme adds a layer of complexity to his character, showing a man driven by both rational inquiry and spiritual conviction.