<p>The scientific and technological underpinnings of microfluidic paper–based analytical devices (μPADs), a field initiated by Whitesides’ research group in 2007, pertain to the design and fabrication of analytical devices composed of paper or other porous membranes that manipulate minute fluid volumes (10⁻⁶ to 10⁻⁹ L) through the principle of capillary action. While the employment of paper in the fabrication of microfluidic devices for analytical purposes confers numerous advantages, it is imperative to acknowledge the challenges that must be surmounted to ensure the reliability and dependability of the industry in the realm of point-of-care testing (POCT). This review delineates the evolution of paper in analytical chemistry, from early chromatographic separations to modern μPADs, followed by an exhaustive examination of the challenges currently confronting researchers who utilize μPADs as analytical instruments. The methods to surmount these challenges will be expounded by presenting numerous real-world applications, predominantly in the health sciences domain.</p> Graphical Abstract <p></p>