A Shot in the Arm by Wilco is a reflective and introspective song that delves into themes of self-medication, personal struggles, and the search for meaning in life. The lyrics explore the idea of attempting to find solace and escape through various means, whether it be love, substance use, or other external sources. A key theme is the yearning for change and the recognition that a transformative 'shot in the arm' might be needed to overcome inner turmoil. Poignant lyrics such as 'What you once were isn't what you want to be anymore' highlight the internal conflict and desire for growth.