Although the last decade in electron microscopy has seen tremendous gains in image resolution, new challenges in the field have come to the forefront. First, new ultra-sensitive instruments bring about unprecedented environmental specifications and facility needs for their optimal use. Second, in the quest for higher spatial resolutions, the importance of developing and sharing crucial expertise—from sample preparation to scientific vision—has perhaps been deemphasized. Finally, for imaging to accelerate discoveries related to large scientific and societal problems, in situ capabilities that replicate real-world process conditions are often required to deliver necessary information. This decade, these are among the hurdles leaders in the field are striving to overcome.