A unique challenge for data analysis with the Laser Interferometer Space Antenna (LISA) is that the noise backgrounds from instrumental noise and astrophysical sources will change significantly over both the year and the entire mission. Variations in the noise levels will be on time scales comparable to, or shorter than, the time most signals spend in the detector's sensitive band. The variation in the amplitude of the galactic stochastic GW background from galactic binaries as the antenna pattern rotates relative to the galactic center is a particularly significant component of the noise variation. LISA's sensitivity to different source classes will therefore vary as a function of sky location and time. The variation will impact both overall signal-to-noise and the efficiency of alerts to EM observers to search for multi-messenger counterparts.