We develop two methods for estimating the power spectrum, C_l, of the cosmic microwave background (CMB) from data and apply them to the COBE/DMR and Saskatoon datasets. One method involves a direct evaluation of the likelihood function, and the other is an estimator that is a minimum-variance weighted quadratic function of the data. Applied iteratively, the quadratic estimator is not distinct from likelihood analysis, but is rather a rapid means of finding the power spectrum that maximizes the likelihood function. Our results bear this out: direct evaluation and quadratic estimation converge to the same C_ls. The quadratic estimator can also be used to directly determine cosmological parameters and their uncertainties. While the two methods both require O(N^3) operations, the quadratic is much faster, and both are applicable to datasets with arbitrary chopping patterns and noise correlations. We also discuss approximations that may reduce it to O(N^2) thus making it practical for forthcoming megapixel datasets.