Portrayals of human isolation in fiction have traditionally been examined using conventional literary forms. Some authors, however, have approached it using innovative literary techniques. The aim of this thesisis to analyse how two of those authors, David Markson and Don DeLillo, have done so and to extrapolate from a selection of their works how literary experimentation can be utilised for the examination of isolation. The critical methodology used for this study is three-pronged. Firstly, the textual analyses are directed by close readings predicated on the theory that literary form and content are indivisible. Secondly, existing experimental literature research will be utilised for the purpose of wider discussion and context. Thirdly, psychological studies will be incorporated to provide context and insights into the causes and impacts of isolation. The core of this thesis will focus on seven formally experimental novels. The first chapter will focus on a selection of David Markson’s works: Wittgenstein’s Mistress (1988), and the novels that comprise his ‘Notecard Quartet’: Reader’s Block (1996), This Is Not a Novel (2001), Vanishing Point and The Last Novel (2007). The second chapter will focus on two works by Don DeLillo: The Body Artist (2001) and Point Omega (2010). This study reveals that versatility displayed in formal experimentation leads to unexpectedly realistic and insightful portrayals of isolation. A concluding chapter shows just a few examples of the continuing relevance of experimental portrayals of isolation, outlining the links between the works of Markson, DeLillo and three contemporary authors: Alicia Kopf, David Shields and Rebecca Watson.