An increasing number of non-terminal giant eruptions are being observed by modern supernova and transient surveys. Very little is known about the origin of these giant eruptions and their progenitors which are presumably very-massive, evolved stars such as luminous blue variables, hypergiants, and supergiants. Motivated by the small number of progenitors positively associated with these giant eruptions, we have begun a survey of the luminous and evolved massive star populations in several nearby galaxies. We aim to identify the likely progenitors of the giant eruptions, study the spatial variations in the stellar populations, and examine the relationship between massive star populations and their environment.The work presented here is focused on stellar populations in the relatively nearby, giant, spiral galaxy M101 from sixteen archival BVI HST/ACS images. We create a catalog of stars in the direction to M101 with photometric errors < 10% for V < 24.5 and 50% completeness down to V = 26.5 even in regions of high stellar crowding. Using color and magnitude criteria we have identified candidate luminous OB type stars and blue supergiants, yellow supergiants, and red supergiants for future observation. We examine their spatial distributions across the face of M101 and find that the ratio of blue to red supergiants decreases by two orders of magnitude over the radial extent.From our catalog, we derive the the star formation history (SFH) for the stellar populations in five 2' wide annuli by fitting the color-magnitude diagrams. Binning the SFH into time frames corresponding to populations traced by Halpha, far ultraviolet (FUV), and near ultraviolet (NUV) emission, we show that the fraction of stellar populations young enough to contribute in Halpha is 15% " 35% in the inner regions, compared to less than 5% in the outer regions. This provides a sufficient explanation for the lack of Halpha emission at large radii. We also model the blue to red supergiant ratio in our five annuli, examine the effects that a metallicity gradient and variable SFH have on the predicted ratios, and compare to the observed values. We find that the radial behavior of our modeled blue to red supergiant ratios is highly sensitive to both spatial variations in the SFH and metallicity. Incorporating the derived SFH into the modeled ratios, we are able to reproduce the observed values at large radii (low metallicity), but at small radii (high metallicity) the modeled and observed ratios are discrepant. Though photometry has proven to be a powerful tool to identify candidate evolved massive stars and their effects on their host galaxy, spectroscopy is necessary to study the physical properties of individual stars. We observed moderate-resolution optical spectra for 56 of the brightest stars in the direction to M101 using the Multiple Mirror Telescope. We also created light curves for each target using multi-epoch UBV R images from the Large Binocular Telescope. We separate the spectroscopially confirmed members of M101 into four groups: hot supergiants, intermediate supergiants, emission-line stars, and LBVs. Several stars in each group are discussed in detail. Of the spectroscopically confirmed members, we find that eight meet our criterion for variability. We present light curves for the known LBV candidates, V2, V4, and V9, and introduce a new candidate: 9492 14 11998. Additionally, we identify 20 new variables in M101. Lacking spectra, we separated the variables, by their photometric properties, into three groups: hot, intermediate, and cool. We find two hot stars with V -band variability of ±1 magnitude; we flag these stars as LBV candidates. Of the intermediate and cool variables, we identify several stars with low- to moderate-amplitude variability (0.1"0.5 magnitudes).