From the Aztecs meticulously extracting indigo from plants to modern chemist synthesizing fluorophores that emit wavelengths beyond what our eyes can see, humanity has long been captivated by the pursuit of vibrant colors. The near infrared (NIR, 700 –1000 nm) and shortwave infrared (SWIR, 1000 – 2000 nm) have emerged as optimal windows for optical imaging in complex biological systems as these wavelengths overcome penetration-depth and resolution challenges that arise from tissue and organs, enabling high contrast imaging. Polymethine dyes, once used to capture vibrant colors in early photography, have proven themselves to be exceptional, biocompatible, SWIR contrast agents. This dissertation explores different structural modifications imparted to SWIR emissive polymethine dyes, their photophysical properties, and their applications as contrast agents for in vivo optical imaging.